New Pradaxa® (dabigatran etexilate mesylate) Data to be Presented at American College of Cardiology Scientific Session (ACC.14)

RIDGEFIELD, Conn., March 24, 2014 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. today announced that data from three company-sponsored PRADAXA studies will be presented at the American College of Cardiology 63^rd Annual Scientific Session (ACC.14) in Washington, D.C., March 29 to 31, 2014.

An oral presentation will highlight pre-clinical data on the development of a specific antidote to reverse dabigatran in cases of bleeding. The investigational fully humanized antibody fragment, known as the Fab (idarucizumab*), was discovered and is being studied by Boehringer Ingelheim.

Post-hoc analysis of data from the pivotal RE-LY^® trial, presented during a poster session, will describe the use of dabigatran compared to warfarin in patients with atrial fibrillation and valvular heart disease (VHD). PRADAXA is currently approved to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) based on RE-LY, one of the largest stroke prevention studies ever conducted in patients with NVAF. PRADAXA is not currently approved for patients with VHD.

Another poster presentation will provide data from the ongoing long-term GLORIA-AF registry, a worldwide prospective observational study – the largest of its kind – designed to identify factors influencing the selection of antithrombotic treatment to prevent stroke in patients with NVAF and to collect data on associated outcomes in clinical practice. The new data provide the first assessment of baseline characteristics of dabigatran and vitamin K antagonist (VKA) groups of patients in North America.

Further information regarding the data presentations includes:

Oral Presentation

• Sunday, March 30
  Session: Emerging and Procedural Issues in Arrhythmias
  • A Specific Antidote to Dabigatran Reduces Blood Loss in Dabigatran- and Trauma-induced Bleeding in a Pig Model (Lead Author: O. Grottke) [Abstract No. 921-03, 10:45-11:00 a.m., Room 145B]

Poster Presentations

• Saturday, March 29
  Session: Arrhythmias and Clinical EP: State of the Art Anticoagulation for Atrial Fibrillation
  • Comparison of Dabigatran versus Warfarin in Patients with Atrial Fibrillation and Valvular Heart Disease: The RE-LY Trial (Lead Author: M. Ezekowitz) [Abstract No./Poster No: 1109-115, 10:00–10:45 a.m., Hall C]  
    
• Sunday, March 30
  Session: Arrhythmias and Clinical EP: New Observations Affecting Clinical Management
  • The Global Registry Program on Long-Term Oral Anti-thrombotic Treatment In Patients with Atrial Fibrillation (GLORIA-AF): First Assessment of Baseline Characteristics of Dabigatran and VKA Cohorts in North America (Lead Author: K. Rothman) [Abstract No./Poster No: 1217-104, 3:45-4:30 p.m., Hall C]

Additional information about PRADAXA will be available at the Boehringer Ingelheim Pharmaceuticals, Inc. booth #3227 at the ACC Scientific Session.

About Pradaxa^® (dabigatran etexilate mesylate) capsules

Indications and Usage
Pradaxa^® (dabigatran etexilate mesylate) capsules is indicated to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation.

Important Safety Information About PRADAXA

CONTRAINDICATIONS
PRADAXA is contraindicated in patients with:

• active pathological bleeding;
• known serious hypersensitivity reaction (e.g., anaphylactic reaction or anaphylactic shock) to PRADAXA;
• mechanical prosthetic heart valve

WARNINGS & PRECAUTIONS
Increased Risk of Stroke with Discontinuation of PRADAXA
Discontinuing PRADAXA in absence of adequate alternative anticoagulation increases the risk of thrombotic events.  If PRADAXA must be discontinued for a reason other than pathological bleeding, consider coverage with another anticoagulant.

Risk of Bleeding

• PRADAXA increases the risk of bleeding and can cause significant and, sometimes, fatal bleeding. Promptly evaluate any signs or symptoms of blood loss (e.g., a drop in hemoglobin and/or hematocrit or hypotension). Discontinue PRADAXA in patients with active pathological bleeding.
• Risk factors for bleeding include concomitant use of medications that increase the risk of bleeding (e.g., anti-platelet agents, heparin, fibrinolytic therapy, and chronic use of NSAIDs). PRADAXA's anticoagulant activity and half-life are increased in patients with renal impairment.
• A specific reversal agent for dabigatran is not available. Hemodialysis can remove dabigatran; however clinical experience for hemodialysis as a treatment for bleeding is limited.  Activated prothrombin complex concentrates, recombinant Factor VIIa, or concentrates of factors II, IX or X may be considered but their use has not been evaluated.  Protamine sulfate and vitamin K are not expected to affect dabigatran anticoagulant activity.  Consider administration of platelet concentrates where thrombocytopenia is present or long-acting antiplatelet drugs have been used.

Thromboembolic and Bleeding Events in Patients with Prosthetic Heart Valves
The safety and efficacy of PRADAXA in patients with bileaflet mechanical prosthetic heart valves (recently implanted or implanted more than 3 months prior to enrollment) was evaluated in the phase 2 RE-ALIGN trial.  RE-ALIGN was terminated early because of significantly more thromboembolic events (valve thrombosis, stroke, transient ischemic attack, and myocardial infarction) and an excess of major bleeding (predominantly post-operative pericardial effusions requiring intervention for hemodynamic compromise) for PRADAXA vs warfarin.  Therefore, the use of PRADAXA is contraindicated in patients with mechanical prosthetic valves.

Use of PRADAXA for the prophylaxis of thromboembolic events in patients with AFib in the setting of other forms of valvular heart disease, including bioprosthetic heart valve, has not been studied and is not recommended.

Effect of P-gp Inducers & Inhibitors on Dabigatran Exposure
The concomitant use of PRADAXA with P-gp inducers (e.g., rifampin) reduces exposure to dabigatran and should generally be avoided.  P-gp inhibition and impaired renal function are major independent factors in increased exposure to dabigatran.  Concomitant use of P-gp inhibitors in patients with renal impairment is expected to increase exposure of dabigatran compared to either factor alone.

• For patients with moderate renal impairment (CrCl 30-50 mL/min), consider reducing the dose of PRADAXA to 75 mg twice daily when dronedarone or systemic ketoconazole is coadministered with PRADAXA.
• For patients with severe renal impairment (CrCl 15-30 mL/min), avoid concomitant use of PRADAXA and P-gp inhibitors.

ADVERSE REACTIONS
In the pivotal trial comparing PRADAXA to warfarin, the most frequent adverse reactions leading to discontinuation of PRADAXA were bleeding and gastrointestinal (GI) events.

• PRADAXA 150 mg resulted in higher rates of major GI bleeds and any GI bleeds compared to warfarin.
• In patients >75 years of age, the risk of major bleeding may be greater with PRADAXA than with warfarin.
• Patients on PRADAXA 150 mg had an increased incidence of GI adverse reactions.
• These were commonly dyspepsia (including abdominal pain upper, abdominal pain, abdominal discomfort, and epigastric discomfort) and gastritis-like symptoms (including GERD, esophagitis, erosive gastritis, gastric hemorrhage, hemorrhagic gastritis, hemorrhagic erosive gastritis, and GI ulcer).  Drug hypersensitivity reactions were reported in < 0.1% of patients receiving PRADAXA.

Other Measures Evaluated
In the pivotal trial, a higher rate of clinical myocardial infarction was reported in patients who received PRADAXA (0.7 per 100 patient-years for 150 mg dose) than in those who received warfarin (0.6).

Please see full Prescribing Information including Boxed WARNING, and Medication Guide.

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About Boehringer Ingelheim Pharmaceuticals, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 140 affiliates and more than 46,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.

As a central element of its culture, Boehringer Ingelheim has a demonstrated commitment to corporate social responsibility. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim's endeavors.

In 2012, Boehringer Ingelheim achieved net sales of about $19.1 billion (14.7 billion euro). R&D expenditure in the business area Prescription Medicines corresponds to 22.5% of its net sales.

For more information please visit www.us.boehringer-ingelheim.com/

PRADAXA^® is a registered trademark of Boehringer Ingelheim Pharma GmBH and Co. KG and used under license.

RE-LY^® is a registered service mark of Boehringer Ingelheim International GmbH and used under license.

GLORIA™-AF is a trademark of Boehringer Ingelheim International GmbH (BII) and is used in the US by Boehringer Ingelheim Pharmaceuticals, Inc. under license from BII.

* Idarucizumab is the proposed International Nonproprietary Name (pINN).

SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.